Tegaserod Maleate

Chemistry, Mechanism of Action, and Pharmacological Properties Tegaserod (zelnorm), an aminoguanidine indole, is structurally related to serotonin and is a partial 5-HT4 agonist with negligible affinity for other receptor subtypes. Tegaserod has multiple effects on the GI tract. It stimulates motility and accelerates transit in the esophagus, stomach, small bowel, and ascending colon. It also stimulates chloride secretion. The clinical efficacy of tegaserod has been shown for male and female patients with constipation-predominant irritable bowel syndrome (see below). In patients with constipation, tegaserod results in mild-to-modest improvement in stool frequency, with less consistent effects on other parameters such as stool form, bloating, and pain. The absolute improvement is modest at best. It is not clear that the drug has any greater efficacy in this regard than other agents used for constipation.

Tegaserod is available for oral administration in 2-mg and 6-mg tablets and is approved for use in women with constipation-dominant irritable bowel syndrome at a dose of 6 mg twice daily. Tegaserod also is approved for the treatment of chronic constipation.

After oral administration, tegaserod is partially absorbed from the gut, reaching peak plasma levels after ~1 hour. Absorption of tegaserod is best on an empty stomach. Once in circulation, tegaserod is ~98% bound to plasma proteins. Tegaserod is degraded by acid hydrolysis before absorption from the stomach, and by oxidation and glucuronidation in the liver to three inactive N-glucuronide metabolites. Approximately two-thirds of the orally administered dose of tegaserod is excreted unchanged in feces, with the remainder excreted in urine; the drug has a t122 of ~11 hours.

Diarrhea and headache are the most common side effects of tegaserod, occurring in ~10% of patients. Tegaserod does not appear to have any clinically relevant drug-drug interactions. No dosage adjustment is required in elderly patients or those with mild-to-moderate hepatic or renal impairment, but tegaserod should not be used in patients with severe hepatic or renal impairment.

Motilin, a 22-amino acid peptide hormone found in the GIM cells and some enterochromaffin cells of the upper small bowel, is a potent contractile agent of the upper GI tract. The effects of motilin can be mimicked by erythromycin and by other macrolide antibiotics (see Chapter 46), including oleandomycin, azithromycin, and clarithromycin.

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.